b'10 Carnegie Science|Fall 2020Gut Bacteriaand Their Effect on UsH undreds to thousands ofQUANTIFYING ROLE OF INTERSPECIES INTERACTIONS ON ANTIBIOTIC SENSTIVITYmicrobial species live in our guts, the human microbiome. They affect our health and longevity. But its difficult to untangle the many waysIN ISOLATIONthat these different species interact with and influence each other and us. Two recent studies from Will Ludingtons lab, with collaborators, have discovered a newAMOUNT OF ANTIBIOTICform of antibiotic tolerance in the complex gut ecosystem and they developed a new technology to visualize the guts of livingIN COMMUNITIESfruit flies in real time for the first time. The fruit fly makes an excellent model because, unlike the humanThe efficacy of antibiotics often differs between the lab and clinic. Interactions with other bacteria in nature can change microbiome, it consists of few bacterialthe susceptibility of certain species to antibiotics. Here the orange bacteria can tolerate higher antibiotic concentration when grown together with the green bacteria (bottom) than when grown in isolation (top). Each blue circle represents a speciesideal for studying multispeciesculture grown with a different antibiotic concentration. The antibiotic concentration increases from left to right. biochemical interactions. Image courtesy Navid Marvi and Andrs Aranda-DazAntibiotics and the GutAlthough its difficult to study thethan they would on their own. Tolerance can microbiome under normal circumstances,be dangerous, however, because this delay it becomes much more complex whenincreases the risk that full-on resistance to antibiotics are introduced to see how thesethe antibiotic could evolve. vital communities are biochemicallyNormally, tolerance occurs when a cell impacted. slows its metabolism in response to When a doctor prescribes antibiotics,antibiotic exposure, explained Ludington. it sets up a multifaceted experiment inBut in this case, the tolerance is actually your gastrointestinal system, explainedImage courtesy iStockphoto.com/magicmine associated with increased metabolism. Ludington. What can this teach us aboutIt turns out that Acetobacterthe molecular principles of species consumes interactions in nature? The simplicity of the fruit flythe lactic acid that is excreted as waste by microbiome makes it the perfect vehicleneighboring LactobacillusLudington and Stanford Universitys, providing a K.C. Huang set out to answer this questionfor revealing how this multispeciesfitness advantage to both species and and discovered a new form of antibioticbiochemical interplay is altered by thetriggering the tolerance the team discovered. tolerance. eLife introduction of antibiotics.We dont know exactly how it happenspublished their findings.We found that interactions betweenyet, but we think the two bacterial species We really wanted to understand howspecies in the gut microbiome ecosystemboth know when the other type of cell is an antibiotics targeting of specificinfluence the effectiveness of antibioticsthere and respond appropriately, said physiological processes impacts theat killing off an individual species withinBenjamin Obadia of the University of metabolic interactions and sharing ofthis community, as well as the entireCalifornia, Berkeley. These mechanisms are resources that occurs between bacterialcommunitys metabolism, said Huang.probably evolved from living together, and species within a community, said leadThe researchers demonstrated thatwe wouldnt have seen them if we studied author Andrs Aranda-Daz of Stanford.when a type of bacterium from the fruit flythe two species in isolation. This is especially important because inmicrobiome called Lactobacillus The teams work shows that the nature bacteria live in diverse communities.which are also found in yogurtis grownmicrobiome can be an important tool for together with a vinegar-producing flyunderstanding the relationships within SUPPORT: bacterium called Acetobacter communities of bacteria in the natural world , it is less The National Institutes of Health, Nationalsusceptible to death by antibiotics.on a biochemical level.Science Foundation, Allen Discovery Center for Systems Modeling of Infection, Chan Zuckerberg,This is a newfound category ofIt also illustrates that gut microbiome Howard Hughes Medical Institute, and Stanfordantibiotic tolerance, meaning that cells diehealth should be considered whenever Universitys Bio-X supported this work. much more slowly when found togetherantibiotics are prescribed, added Ludington.'